New Insights into the Immunity to Human Fungal Infections

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 11714

Special Issue Editor


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Guest Editor
Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London, UK
Interests: Candida; Scedosporium/Lomentospora; innate immunity; epithelial cells; macrophages; host-microbe interactions

Special Issue Information

Dear Colleagues,

Fungal diseases are a growing health problem worldwide, with unacceptable high morbidity and mortality rates, especially in immunocompromised hosts. Fungal infections range from superficial, mucosal diseases to systemic, life-threatening infections, and they affect a wide variety of body areas. Notably, there are also many fungal microbes present in healthy human microbiota (namely, mycobiota), with some eventually developing into pathobionts.

For these reasons, antifungal immunity is so diverse and complex that, even though there have been great advances in our knowledge in the last decades, gaps in understanding still remain. Understanding the complexity of immune responses to fungi is of paramount importance to overcoming the numerous challenges associated with the management of these infections. Moreover, studying the interplay between commensal fungi and their host is essential to understand their roles in physiology and tissue homeostasis. However, there are still many challenges that need to be addressed in the field.

Therefore, for this Special Issue in Fungi, we are inviting the submission of original research articles, review papers and short communications. Potential topics include (but are not limited to):

  • Innate immune responses;
  • Adaptive immune responses;
  • Immunity to pathogens and fungal commensals/pathobionts;
  • Fungal interactions with non-immune cells (e.g., epithelial cells, endothelial cells, etc.);
  • Impact of antifungal treatment on immune recognition;
  • Omics-technology-based studies of host–fungus interactions;
  • Metabolism/immunometabolism;
  • Medical case reports;
  • Fungal infection models.

We look forward to receiving your contributions to this Special Issue.

Dr. Aize Pellon
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • fungal infections
  • antifungal immunity
  • innate
  • adaptive
  • mucosal
  • systemic
  • Candida
  • Aspergillus
  • Fusarium
  • Cryptococcus
  • Mucorales
  • Scedosporium

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Published Papers (5 papers)

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Research

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21 pages, 6304 KiB  
Article
Mitochondrial Protease Oct1p Regulates Mitochondrial Homeostasis and Influences Pathogenicity through Affecting Hyphal Growth and Biofilm Formation Activities in Candida albicans
by Xiaoxiao Zhu, Feng Jin, Guangyuan Yang, Tian Zhuang, Cangcang Zhang, Hanjing Zhou, Xiaojia Niu, Hongchen Wang and Daqiang Wu
J. Fungi 2024, 10(6), 391; https://doi.org/10.3390/jof10060391 - 30 May 2024
Viewed by 955
Abstract
Mitochondria, as the core metabolic organelles, play a crucial role in aerobic respiration/biosynthesis in fungi. Numerous studies have demonstrated a close relationship between mitochondria and Candida albicans virulence and drug resistance. Here, we report an octapeptide-aminopeptidase located in the mitochondrial matrix named Oct1p. [...] Read more.
Mitochondria, as the core metabolic organelles, play a crucial role in aerobic respiration/biosynthesis in fungi. Numerous studies have demonstrated a close relationship between mitochondria and Candida albicans virulence and drug resistance. Here, we report an octapeptide-aminopeptidase located in the mitochondrial matrix named Oct1p. Its homolog in the model fungus Saccharomyces cerevisiae is one of the key proteins in maintaining mitochondrial respiration and protein stability. In this study, we utilized evolutionary tree analysis, gene knockout experiments, mitochondrial function detection, and other methods to demonstrate the impact of Oct1p on the mitochondrial function of C. albicans. Furthermore, through transcriptome analysis, real-time quantitative PCR, and morphological observation, we discovered that the absence of Oct1p results in functional abnormalities in C. albicans, affecting hyphal growth, cell adhesion, and biofilm formation. Finally, the in vivo results of the infection of Galleria mellonella larvae and vulvovaginal candidiasis in mice indicate that the loss of Oct1p led to the decreased virulence of C. albicans. In conclusion, this study provides a solid theoretical foundation for treating Candida diseases, developing new targeted drugs, and serves as a valuable reference for investigating the connection between mitochondria and virulence in other pathogenic fungi. Full article
(This article belongs to the Special Issue New Insights into the Immunity to Human Fungal Infections)
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14 pages, 1099 KiB  
Article
The IFSD Score—A Practical Prognostic Model for Invasive Fungal Spondylodiscitis
by Chao-Chun Yang, Ming-Hsueh Lee, Chia-Yen Liu, Meng-Hung Lin, Yao-Hsu Yang, Kuo-Tai Chen and Tsung-Yu Huang
J. Fungi 2024, 10(1), 61; https://doi.org/10.3390/jof10010061 - 12 Jan 2024
Viewed by 1415
Abstract
Objectives: Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. The previous literature revealed limited data concerning its outcomes. This study aimed to establish a risk-scoring system to predict the one-year mortality rate of this disease. Methods: A total [...] Read more.
Objectives: Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. The previous literature revealed limited data concerning its outcomes. This study aimed to establish a risk-scoring system to predict the one-year mortality rate of this disease. Methods: A total of 53 patients from a multi-centered database in Taiwan were included in this study. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to one-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic (ROC) curve was used to express the performance of our IFSD scoring model. Results: Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or <0.4 103/µL, hemoglobin < 8 g/dL, and evidence of candidemia. One-year mortality rates for patients with IFSD scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the ROC curve was 0.823. Conclusions: We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of one-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used. Full article
(This article belongs to the Special Issue New Insights into the Immunity to Human Fungal Infections)
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10 pages, 2224 KiB  
Communication
Novel Pneumocystis Antigens for Seroprevalence Studies
by Dora Pungan, Jia Fan, Guixiang Dai, Mst Shamima Khatun, Monika L. Dietrich, Kevin J. Zwezdaryk, James E. Robinson, Samuel J. Landry and Jay K. Kolls
J. Fungi 2023, 9(6), 602; https://doi.org/10.3390/jof9060602 - 24 May 2023
Viewed by 2300
Abstract
Pneumocystis jirovecii is the most common cause of fungal pneumonia in children under the age of 2 years. However, the inability to culture and propagate this organism has hampered the acquisition of a fungal genome as well as the development of recombinant antigens to [...] Read more.
Pneumocystis jirovecii is the most common cause of fungal pneumonia in children under the age of 2 years. However, the inability to culture and propagate this organism has hampered the acquisition of a fungal genome as well as the development of recombinant antigens to conduct seroprevalence studies. In this study, we performed proteomics on Pneumocystis-infected mice and used the recent P. murina and P. jirovecii genomes to prioritize antigens for recombinant protein expression. We focused on a fungal glucanase due to its conservation among fungal species. We found evidence of maternal IgG to this antigen, followed by a nadir in pediatric samples between 1 and 3 months of age, followed by an increase in prevalence over time consistent with the known epidemiology of Pneumocystis exposure. Moreover, there was a strong concordance of anti-glucanase responses and IgG against another Pneumocystis antigen, PNEG_01454. Taken together, these antigens may be useful tools for Pneumocystis seroprevalence and seroconversion studies. Full article
(This article belongs to the Special Issue New Insights into the Immunity to Human Fungal Infections)
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Review

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19 pages, 1240 KiB  
Review
Mucosal Immunity to Gut Fungi in Health and Inflammatory Bowel Disease
by Sean L. Carlson, Liya Mathew, Michael Savage, Klaartje Kok, James O. Lindsay, Carol A. Munro and Neil E. McCarthy
J. Fungi 2023, 9(11), 1105; https://doi.org/10.3390/jof9111105 - 14 Nov 2023
Cited by 3 | Viewed by 3504
Abstract
The gut microbiome is a diverse microbial community composed of bacteria, viruses, and fungi that plays a major role in human health and disease. Dysregulation of these gut organisms in a genetically susceptible host is fundamental to the pathogenesis of inflammatory bowel disease [...] Read more.
The gut microbiome is a diverse microbial community composed of bacteria, viruses, and fungi that plays a major role in human health and disease. Dysregulation of these gut organisms in a genetically susceptible host is fundamental to the pathogenesis of inflammatory bowel disease (IBD). While bacterial dysbiosis has been a predominant focus of research for many years, there is growing recognition that fungal interactions with the host immune system are an important driver of gut inflammation. Candida albicans is likely the most studied fungus in the context of IBD, being a near universal gut commensal in humans and also a major barrier-invasive pathogen. There is emerging evidence that intra-strain variation in C. albicans virulence factors exerts a critical influence on IBD pathophysiology. In this review, we describe the immunological impacts of variations in C. lbicans colonisation, morphology, genetics, and proteomics in IBD, as well as the clinical and therapeutic implications. Full article
(This article belongs to the Special Issue New Insights into the Immunity to Human Fungal Infections)
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15 pages, 1484 KiB  
Review
Genetic and Other Determinants for the Severity of Coccidioidomycosis: A Clinician’s Perspective
by John N. Galgiani, Amy P. Hsu, Daniel A. Powell, Jatin M. Vyas and Steven M. Holland
J. Fungi 2023, 9(5), 554; https://doi.org/10.3390/jof9050554 - 11 May 2023
Cited by 8 | Viewed by 2308
Abstract
The endemic fungal infection, coccidioidomycosis, occurs after inhalation of one or very few Coccidioides spp. spores. Infections produce diverse clinical manifestations, ranging from insignificant to extremely destructive, even fatal. Approaches to understanding this range of consequences have traditionally categorized patients into a small [...] Read more.
The endemic fungal infection, coccidioidomycosis, occurs after inhalation of one or very few Coccidioides spp. spores. Infections produce diverse clinical manifestations, ranging from insignificant to extremely destructive, even fatal. Approaches to understanding this range of consequences have traditionally categorized patients into a small number of groups (asymptomatic, uncomplicated self-limited, fibro-cavitary, and extra-thoracic disseminated) and then looked for immunologic differences among them. Recently, variants within genes of innate pathways have been found to account, in part, for infections that result in disseminated disease. This discovery raises the very attractive theory that, in patients without severe immunosuppression, much of the disease spectrum can be accounted for by various combinations of such deleterious variants in innate pathways. In this review, we summarize what is known about genetic determinants that are responsible for the severity of coccidioidal infections and how complex innate genetic differences among different people might account for the spectrum of disease observed clinically. Full article
(This article belongs to the Special Issue New Insights into the Immunity to Human Fungal Infections)
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